With the widespread use of mass spectrometry in the fields of food safety, pharmaceutical research and biochemical applications, it has become increasingly important to be able to mass analyze samples directly under atmospheric conditions for rapid identification of unknown samples.
The emergence of electrospray ionization (ESI) and atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) have partially solved the issue for ionizing analytes in the liquid and solid form, respectively, under atmospheric pressure. However, to analyze samples from solid surface by AP-MALDI a certain matrix has to be pre-mixed with the analytes on the surface, which makes it difficult for rapid screening of large quantity of solid samples. In order to overcome this limitation many direct analysis methods for solid samples based upon various principles have been proposed and verified. Science, 2004, 306, 471-273. introduced the first direct analysis method which involves using electrosprayed droplets to desorb/ionize solid samples directly from surface and send the ions formed into a mass spectrometer. The speed and simplicity of this method greatly enhanced the applicability of mass spectrometry to direct analysis in field.
Soon after the DESI technique was announced, several other direct analysis methods also achieved success. For example, Anal. Chem. 2005, 77, 2297-2302. introduced a method called direct analysis in real time (DART) which replaced the electrosprayed droplets with metastable He atoms as the means to desorb analytes from solid surface. In some other related examples as described in the U.S. Pat. Appl. 20070187589 and Anal. Chem. 2007, 79, 7867-7872, methods such as desorption atmospheric pressure chemical ionization (DAPCI) and desorption atmospheric pressure photoionization (DAPPI) have been described, respectively. The latter two methods complement the DESI method to some extend due to their capability for ionization relatively less polar species.
However, the methods mentioned above all use either molecular or ion beam to desorb analytes from surface, and therefore it is very difficult to control the area of desorption and to perform chemical imaging of the sample surface. To overcome this limitation Rapid Commun. Mass Spectrom. 2005, 19, 3701-3704. introduced an electrospray assisted laser desorption (ELDI) method which greatly enhanced the spatial resolution of the sampling process by using laser as the desorption means. In this method the sampling area limited by the size of the laser spot can be accurately defined. At the same time, the electrospray process involved in this technique is advantageous for analyzing polar species. A similar technique described in Rapid Commun. Mass Spectrom. 2002, 16, 681-685. also used laser as desorption means but used chemical ionization to ionize the desorbed analytes in the gas phase, which is complementary to the ELDI technique since it is suitable for analyzing less polar and relatively small molecules. Nevertheless, the non-polar analytes in the atmosphere still remained to be ionized more efficiently by photoionization, since high energy photons can directly ionize the analytes in the gas phase without charge transfer process. While the DAPPI technique uses UV photons for ionization, again the heated gas stream as desorption means lacks high spatial resolution for chemical imaging application.
Although a Chinese Pat. publication CN101216459A has described a technique involving laser desorbing and post UV ionizing analytes from surface, the entire process in this method occurred in the vacuum. This largely limits the use of the ion source for the goal of direct analysis due to the slow and inconvenient process of vacuum loading.
One of the goals of this invention is to combine the merits of the laser desorption and the photoionization techniques so that the laser based ionization methods can cover a broader range of chemical classes. At the same time, this invention will circumvent the limitation of the slow vacuum loading process by performing all the ionization process under ambient conditions. Another goal of this invention is to combine the laser desorption photoionization method described in this invention with ELDI with the aim of analyzing chemicals in different classes simultaneously, by which frequent switching among different types of ion sources can be avoided.